Non-Squamous Non-Small Cell Lung Cancer
Conditions
Brief summary
This 2 arm study will assess the efficacy and safety of Tarceva plus gemcitabine, compared with gemcitabine alone, in the treatment of chemotherapy-naive patients with advanced non-small cell lung cancer. Patients will be randomized to receive either Tarceva 150mg po daily plus gemcitabine on days 1, 8, 15 and every 4 weeks subsequently, or with gemcitabine monotherapy. The anticipated time on study treatment is until disease progression, and the target sample size is 100-500 individuals.
Interventions
DRUGErlotinib
150 mg po daily
DRUGGemcitabine
As prescribed
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* adult patients, \>=18 years of age; * non-small cell lung cancer, stage IIIb (with effusion) or stage IV with measurable disease ; * ECOG PS 2; * adequate organ function.
Exclusion criteria
* prior chemotherapy or systemic anti-tumor therapy; * hypersensitivity to erlotinib; * any condition contraindicating the use of the study medication and/or impairing the interpretation of results and/or leading to treatment-related complications.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | Up to 2 years | Progression free survival was defined as the interval between the day of randomization and the date of the first documentation of disease progression or date of death (from any cause), whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate | Up to 2 years | Disease control rate was defined as the percentage of participants who have any evidence of confirmed objective CR or PR or Stable disease (SD) (where SD was maintained for 8 weeks), as assessed by the RECIST version 1.0 criteria. As per the RECIST Version 1.0 CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum of the LD. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum of the LD since the treatment started. PD is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum of the LD recorded since the treatment started or the appearance of one or more new lesions. |
| Duration of Response | Up to 2 years | Duration of response was defined as the interval between the date of CR or PR was first recorded to the date on which progressive disease was first noted or date of death. |
| Overall Survival | Up to 2 years | Overall survival was defined as the interval between the date of randomization to the date of death from any cause. |
| Objective Response Rate | Up to 2 years | Objective response rate was defined as the percentage of participants who have any evidence of confirmed objective of complete response (CR) + partial response (PR), as assessed by the Response Evaluation Criteria In Solid Tumors (RECIST version 1.0) criteria. As per the RECIST Version 1.0 CR is defined as disappearance of all target lesions and PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of the LD. |
| Mean Change in Blood Pressure From Baseline | Baseline (Day -14 to Day 0), Cycle 1 (Days 1, 8, 15 and 22), Cycle 2 (Days 1, 8, 15 and 22), Cycle 3 (Days 1, 8, and 15), Cycle 4 (Days 1, 8, and 15), Cycle 5 (Days 1, 8, and 15), Cycle 6 (Days 1, 8, and 15) | Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded as vital parameters in this study. Mean change in SBP and DBP from Baseline for each cycle calculated as Day 1 of each cycle value minus baseline value. |
| Mean Change in Body Temperature From Baseline | Baseline (Day -14 to Day 0), Cycle 1 (Days 1, 8, 15 and 22), Cycle 2 (Days 1, 8, 15 and 22), Cycle 3 (Days 1, 8, and 15), Cycle 4 (Days 1, 8, and 15), Cycle 5 (Days 1, 8, and 15), Cycle 6 (Days 1, 8, and 15) | Mean change in body temperature from Baseline for each cycle calculated as Day 1 of each cycle value minus baseline value. |
| Mean Change in Pulse Rate From Baseline | Baseline (Day -14 to Day 0), Cycle 1 (Days 1, 8, 15 and 22), Cycle 2 (Days 1, 8, 15 and 22), Cycle 3 (Days 1, 8, and 15), Cycle 4 (Days 1, 8, and 15), Cycle 5 (Days 1, 8, and 15), Cycle 6 (Days 1, 8, and 15) | Mean change in pulse rate from Baseline for each cycle calculated as Day 1 of each cycle value minus Baseline value |
Countries
Australia
Participant flow
Recruitment details
A total of 17 chemo-naïve participants with Non-Small Cell Lung Cancer (NSCLC) Stage IIIB with pleural effusion or stage IV and a Eastern Cooperative Oncology Group performance status 2 (PS 2) were recruited. The study was conducted from 24 August 2007 to 14 February 2009 at 14 Centers in Australia.
Pre-assignment details
Total 17 participants were enrolled; however the data was available for 16 participants. One participant in the gemcitabine arm withdrew consent before receiving treatment.
Participants by arm
| Arm | Count |
|---|---|
| Gemcitabine Participants received Gemcitabine 1000 (mg/m\^2)/day, IV on Days 1, 8, 15 and every 4 weeks for 6 cycles | 9 |
| Erlotinib + Gemcitabine Participants received Erlotinib 150 mg/day orally as a continuous schedule with Gemcitabine 1000 (mg/m\^2)/day, IV on Days 1, 8, 15 and every 4 weeks for 6 cycles | 8 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 |
| Overall Study | Death | 1 | 1 |
| Overall Study | Disease Progression | 2 | 2 |
| Overall Study | Other Reasons | 3 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Gemcitabine | Erlotinib + Gemcitabine | Total |
|---|---|---|---|
| Age, Continuous | 71.6 years STANDARD_DEVIATION 12.94 | 76.8 years STANDARD_DEVIATION 4.17 | 74.0 years STANDARD_DEVIATION 9.92 |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 7 Participants | 5 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 8 | 8 / 8 |
| serious Total, serious adverse events | 5 / 8 | 6 / 8 |
Outcome results
Primary
Progression Free Survival
Progression free survival was defined as the interval between the day of randomization and the date of the first documentation of disease progression or date of death (from any cause), whichever occurs first.
Time frame: Up to 2 years
Population: Per protocol (PP) population included all randomized participants who received at least one dose of study medication and had at least one post baseline tumor assessment or record of death.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gemcitabine | Progression Free Survival | 23.3 Week |
| Erlotinib + Gemcitabine | Progression Free Survival | 24.4 Week |
p-value: 0.364495% CI: [0.483, 7.027]Log Rank
Secondary
Disease Control Rate
Disease control rate was defined as the percentage of participants who have any evidence of confirmed objective CR or PR or Stable disease (SD) (where SD was maintained for 8 weeks), as assessed by the RECIST version 1.0 criteria. As per the RECIST Version 1.0 CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum of the LD. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum of the LD since the treatment started. PD is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum of the LD recorded since the treatment started or the appearance of one or more new lesions.
Time frame: Up to 2 years
Population: PP population included all randomized participants who received at least one dose of study medication and had at least one post baseline tumor assessment or record of death.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gemcitabine | Disease Control Rate | 50 Percentage of participants |
| Erlotinib + Gemcitabine | Disease Control Rate | 85.7 Percentage of participants |
Secondary
Duration of Response
Duration of response was defined as the interval between the date of CR or PR was first recorded to the date on which progressive disease was first noted or date of death.
Time frame: Up to 2 years
Population: PP population included all randomized participants received at least one dose of study medication and had at least one post baseline tumor assessment or record of death. Participants available at the time of evaluation of duration of response were included in the analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Erlotinib + Gemcitabine | Duration of Response | 16.3 Week |
Secondary
Mean Change in Blood Pressure From Baseline
Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded as vital parameters in this study. Mean change in SBP and DBP from Baseline for each cycle calculated as Day 1 of each cycle value minus baseline value.
Time frame: Baseline (Day -14 to Day 0), Cycle 1 (Days 1, 8, 15 and 22), Cycle 2 (Days 1, 8, 15 and 22), Cycle 3 (Days 1, 8, and 15), Cycle 4 (Days 1, 8, and 15), Cycle 5 (Days 1, 8, and 15), Cycle 6 (Days 1, 8, and 15)
Population: Safety population included all participants who received at least one dose or infusion of study treatment and had a safety assessment performed at Baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gemcitabine | Mean Change in Blood Pressure From Baseline | DBP at Cycle 6 (n=1, 2) | 5.00 mm Hg | — |
| Gemcitabine | Mean Change in Blood Pressure From Baseline | SBP at Cycle 1 (n=8, 8) | 3.00 mm Hg | Standard Deviation 6.34 |
| Gemcitabine | Mean Change in Blood Pressure From Baseline | DBP at Cycle 1 (n=8, 8) | -6.87 mm Hg | Standard Deviation 9.41 |
| Gemcitabine | Mean Change in Blood Pressure From Baseline | SBP at Cycle 2 (n=7, 6) | -4.85 mm Hg | Standard Deviation 8.33 |
| Gemcitabine | Mean Change in Blood Pressure From Baseline | DBP at Cycle 2 (n=7, 6) | -10.71 mm Hg | Standard Deviation 9.44 |
| Gemcitabine | Mean Change in Blood Pressure From Baseline | SBP at Cycle 3 (n=4, 5) | -9.00 mm Hg | Standard Deviation 8.67 |
| Gemcitabine | Mean Change in Blood Pressure From Baseline | DBP at Cycle 3 (n=4, 5) | -8.25 mm Hg | Standard Deviation 11.89 |
| Gemcitabine | Mean Change in Blood Pressure From Baseline | SBP at Cycle 4 (n=1, 5) | -18.00 mm Hg | — |
| Gemcitabine | Mean Change in Blood Pressure From Baseline | DBP at Cycle 4 (n=1, 5) | -4.00 mm Hg | — |
| Gemcitabine | Mean Change in Blood Pressure From Baseline | SBP at Cycle 5 (n=1, 3) | 28.00 mm Hg | — |
| Gemcitabine | Mean Change in Blood Pressure From Baseline | DBP at Cycle 5 (n=1, 3) | 12.00 mm Hg | — |
| Gemcitabine | Mean Change in Blood Pressure From Baseline | SBP at Cycle 6 (n=1, 2) | 10.00 mm Hg | — |
| Erlotinib + Gemcitabine | Mean Change in Blood Pressure From Baseline | DBP at Cycle 5 (n=1, 3) | 0.66 mm Hg | Standard Deviation 2.51 |
| Erlotinib + Gemcitabine | Mean Change in Blood Pressure From Baseline | DBP at Cycle 6 (n=1, 2) | -0.50 mm Hg | Standard Deviation 2.12 |
| Erlotinib + Gemcitabine | Mean Change in Blood Pressure From Baseline | DBP at Cycle 3 (n=4, 5) | -9.20 mm Hg | Standard Deviation 15.64 |
| Erlotinib + Gemcitabine | Mean Change in Blood Pressure From Baseline | SBP at Cycle 1 (n=8, 8) | -0.87 mm Hg | Standard Deviation 9.4 |
| Erlotinib + Gemcitabine | Mean Change in Blood Pressure From Baseline | SBP at Cycle 5 (n=1, 3) | -1.66 mm Hg | Standard Deviation 12.34 |
| Erlotinib + Gemcitabine | Mean Change in Blood Pressure From Baseline | DBP at Cycle 1 (n=8, 8) | -5.37 mm Hg | Standard Deviation 12.21 |
| Erlotinib + Gemcitabine | Mean Change in Blood Pressure From Baseline | SBP at Cycle 4 (n=1, 5) | -10.20 mm Hg | Standard Deviation 16.52 |
| Erlotinib + Gemcitabine | Mean Change in Blood Pressure From Baseline | SBP at Cycle 2 (n=7, 6) | -17.83 mm Hg | Standard Deviation 9.9 |
| Erlotinib + Gemcitabine | Mean Change in Blood Pressure From Baseline | SBP at Cycle 6 (n=1, 2) | 5.00 mm Hg | Standard Deviation 0 |
| Erlotinib + Gemcitabine | Mean Change in Blood Pressure From Baseline | DBP at Cycle 2 (n=7, 6) | -9.50 mm Hg | Standard Deviation 11.81 |
| Erlotinib + Gemcitabine | Mean Change in Blood Pressure From Baseline | DBP at Cycle 4 (n=1, 5) | -1.60 mm Hg | Standard Deviation 14.32 |
| Erlotinib + Gemcitabine | Mean Change in Blood Pressure From Baseline | SBP at Cycle 3 (n=4, 5) | -17.20 mm Hg | Standard Deviation 19.14 |
Secondary
Mean Change in Body Temperature From Baseline
Mean change in body temperature from Baseline for each cycle calculated as Day 1 of each cycle value minus baseline value.
Time frame: Baseline (Day -14 to Day 0), Cycle 1 (Days 1, 8, 15 and 22), Cycle 2 (Days 1, 8, 15 and 22), Cycle 3 (Days 1, 8, and 15), Cycle 4 (Days 1, 8, and 15), Cycle 5 (Days 1, 8, and 15), Cycle 6 (Days 1, 8, and 15)
Population: Safety population included all participants who received at least one dose/infusion and had at least one safety assessment performed at baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gemcitabine | Mean Change in Body Temperature From Baseline | Cycle 1 (n=8, 8) | -0.02 Fahrenheit | Standard Deviation 0.73 |
| Gemcitabine | Mean Change in Body Temperature From Baseline | Cycle 5 (n=1, 3) | -0.70 Fahrenheit | — |
| Gemcitabine | Mean Change in Body Temperature From Baseline | Cycle 2 (n=7, 6) | 0.14 Fahrenheit | Standard Deviation 0.82 |
| Gemcitabine | Mean Change in Body Temperature From Baseline | Cycle 3 (n=4, 5) | -0.07 Fahrenheit | Standard Deviation 0.68 |
| Gemcitabine | Mean Change in Body Temperature From Baseline | Cycle 4 (n=1, 5) | -0.60 Fahrenheit | — |
| Gemcitabine | Mean Change in Body Temperature From Baseline | Cycle 6 (n=1, 2) | -0.20 Fahrenheit | — |
| Erlotinib + Gemcitabine | Mean Change in Body Temperature From Baseline | Cycle 2 (n=7, 6) | -0.30 Fahrenheit | Standard Deviation 0.4 |
| Erlotinib + Gemcitabine | Mean Change in Body Temperature From Baseline | Cycle 4 (n=1, 5) | -0.24 Fahrenheit | Standard Deviation 0.46 |
| Erlotinib + Gemcitabine | Mean Change in Body Temperature From Baseline | Cycle 5 (n=1, 3) | -0.46 Fahrenheit | Standard Deviation 0.25 |
| Erlotinib + Gemcitabine | Mean Change in Body Temperature From Baseline | Cycle 6 (n=1, 2) | -0.20 Fahrenheit | Standard Deviation 0.98 |
| Erlotinib + Gemcitabine | Mean Change in Body Temperature From Baseline | Cycle 1 (n=8, 8) | -0.012 Fahrenheit | Standard Deviation 0.11 |
| Erlotinib + Gemcitabine | Mean Change in Body Temperature From Baseline | Cycle 3 (n=4, 5) | -0.32 Fahrenheit | Standard Deviation 0.37 |
Secondary
Mean Change in Pulse Rate From Baseline
Mean change in pulse rate from Baseline for each cycle calculated as Day 1 of each cycle value minus Baseline value
Time frame: Baseline (Day -14 to Day 0), Cycle 1 (Days 1, 8, 15 and 22), Cycle 2 (Days 1, 8, 15 and 22), Cycle 3 (Days 1, 8, and 15), Cycle 4 (Days 1, 8, and 15), Cycle 5 (Days 1, 8, and 15), Cycle 6 (Days 1, 8, and 15)
Population: Safety population included all participants who received at least one dose or infusion of study treatment and had a safety assessment performed at baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gemcitabine | Mean Change in Pulse Rate From Baseline | Cycle 4 (n=1, 5) | 18.00 beats per minute | — |
| Gemcitabine | Mean Change in Pulse Rate From Baseline | Cycle 2 (n=7, 6) | 3.00 beats per minute | Standard Deviation 12.19 |
| Gemcitabine | Mean Change in Pulse Rate From Baseline | Cycle 5 (n=1, 3) | -6.00 beats per minute | — |
| Gemcitabine | Mean Change in Pulse Rate From Baseline | Cycle 3 (n=4, 5) | 2.75 beats per minute | Standard Deviation 13.14 |
| Gemcitabine | Mean Change in Pulse Rate From Baseline | Cycle 6 (n= 1, 2) | 4.00 beats per minute | — |
| Gemcitabine | Mean Change in Pulse Rate From Baseline | Cycle 1 (n=8, 8) | 2.37 beats per minute | Standard Deviation 14.31 |
| Erlotinib + Gemcitabine | Mean Change in Pulse Rate From Baseline | Cycle 6 (n= 1, 2) | 6.00 beats per minute | Standard Deviation 0 |
| Erlotinib + Gemcitabine | Mean Change in Pulse Rate From Baseline | Cycle 2 (n=7, 6) | -3.00 beats per minute | Standard Deviation 12.96 |
| Erlotinib + Gemcitabine | Mean Change in Pulse Rate From Baseline | Cycle 3 (n=4, 5) | -1.80 beats per minute | Standard Deviation 7.08 |
| Erlotinib + Gemcitabine | Mean Change in Pulse Rate From Baseline | Cycle 4 (n=1, 5) | 1.80 beats per minute | Standard Deviation 15.33 |
| Erlotinib + Gemcitabine | Mean Change in Pulse Rate From Baseline | Cycle 5 (n=1, 3) | -9.00 beats per minute | Standard Deviation 18.52 |
| Erlotinib + Gemcitabine | Mean Change in Pulse Rate From Baseline | Cycle 1 (n=8, 8) | 3.00 beats per minute | Standard Deviation 5.58 |
Secondary
Objective Response Rate
Objective response rate was defined as the percentage of participants who have any evidence of confirmed objective of complete response (CR) + partial response (PR), as assessed by the Response Evaluation Criteria In Solid Tumors (RECIST version 1.0) criteria. As per the RECIST Version 1.0 CR is defined as disappearance of all target lesions and PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of the LD.
Time frame: Up to 2 years
Population: PP population included all randomized participants who received at least one dose of study medication and had at least one post baseline tumor assessment or record of death.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gemcitabine | Objective Response Rate | 0 Percentage of participants |
| Erlotinib + Gemcitabine | Objective Response Rate | 28.6 Percentage of participants |
Secondary
Overall Survival
Overall survival was defined as the interval between the date of randomization to the date of death from any cause.
Time frame: Up to 2 years
Population: PP population included all randomized participants who received at least one dose of study medication and had at least one post baseline tumor assessment or record of death
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Gemcitabine | Overall Survival | 21.1 Week |
| Erlotinib + Gemcitabine | Overall Survival | 39.0 Week |
p-value: 0.716595% CI: [0.339, 4.824]Log Rank